Development and Validation of Point-of-Care Tests for Tuberculosis

项目总结 结核病(TB)是世界上第二大致命传染病，仅次于 艾滋病毒/艾滋病。有效控制结核病需要及时、准确的诊断，但在地方性疾病中 在各地区，最初的患者管理是基于临床怀疑和低敏感性痰 显微镜。验证性培养检测速度慢、费用高，而且不是常规的可用方法。的确有 目前缺乏早期诊断检测，当与边缘临床实验室结合时 基础设施，可能导致对结核病的诊断不足或过度。前者成功地冲击了 患者结局和阻止二次传播的努力，而后者促进 不必要的治疗和医疗资源的不合理利用。新增结核病人数 在美国确诊的病例仍然很多，很大一部分感染发生在 对于获得医疗保健的机会有限、在外国出生和/或感染艾滋病毒的个人。 我们已经组建了一个由临床医生、结核病专家、免疫学家和化学家组成的团队，以开发一种 新的结核病检测方法。使用表面增强拉曼光谱(SERS)显著降低了 为了达到检测极限，我们建议开发一种廉价、快速、准确的测点 利用多克隆抗体同时进行CARE免疫诊断试验 确定一组已在体内鉴定的结核分枝杆菌靶抗原 活动性感染期间的体液。预计检测结核分枝杆菌抗原的配对试验 无论是血清还是尿液都将显著提高抗原检测的整体灵敏度， 重新定义结核病的管理方式。这一方法有望提供定性和 在各种设置下进行快速、可靠诊断所需的定量数据，使 迅速准确地治疗结核病，并立即采取旨在 避免传染给其他人。该方法的影响被放大，因为SERS平台 通过改变检测序列来适应其他传染病的诊断 抗体。

PROJECT SUMMARY Tuberculosis (TB) is the world's second deadliest infectious disease, overshadowed only by HIV/AIDS. A prompt, accurate diagnosis is required for effective control of TB, but in endemic regions, patient management is initially based upon clinical suspicion and low-sensitivity sputum microscopy. Confirmatory culture testing is slow, costly, and not routinely available. There is currently a lack of early diagnostic tests, which, when combined with marginal clinical laboratory infrastructure, can result in the under- or over-diagnosis of TB. The former impacts successful patient outcomes and efforts to block secondary transmission, while the latter promotes unnecessary treatment and poor utilization of healthcare resources. The number of new TB cases diagnosed in the U.S. remains sizable, with a significant proportion of infections occurring in individuals who have limited access to health care, are foreign-born, and/or are HIV-infected. We have assembled a team of clinicians, TB experts, immunologists, and chemists to develop a new test for TB. Using surface-enhanced Raman spectroscopy (SERS) to significantly lower the limit of detection, we propose the development of an inexpensive, rapid, and accurate point-of- care immunodiagnostic assay utilizing multiplexed monoclonal antibodies to concurrently identify a panel of Mycobacterium tuberculosis target antigens that have been identified in body fluids during active infection. It is anticipated that a paired test to detect M. tuberculosis antigens in both serum and urine will significantly improve the overall sensitivity of antigen detection, redefining the way TB is managed. This approach is expected to provide the qualitative and quantitative data necessary for rapid, reliable diagnosis in a variety of settings, allowing the prompt accurate treatment of TB, as well as immediate infection control measures designed to avert transmission to others. The impact of the approach is amplified as the SERS platform can be adapted to the diagnosis of other infectious diseases by changing the array of detection antibodies.